To advance our understanding of ear development and the underlying molecular and genetic interactions, we are undertaking a forward genetic screen in the amphibian Xenopus tropicalis, a recently introduced genetic model animal. This pilot study reveals several loci involved in ear morphology, otolith formation, and balancing/swimming behavior. Importantly, the major events of X. tropicalis ear morphogenesis can be observed externally in the living embryos, greatly aiding screens for genetic defects. Previous work in ear development has demonstrated that underlying molecular mechanisms are well conserved from human to frog, making genetically amenable and oviparous X. tropicalis an attractive model animal in which to study the causes of hearing and balance anomalies as well as underlying molecular and genetic interactions. Previous screens for inner ear mutants have been done in zebrafish and mouse, and we expect to find both overlapping and different mutations in Xenopus. In this proposal we shall identify and map mutations affecting the ear, and link them to previously known candidate genes, or identify them as new loci involved in ear development. We shall characterize the mutant phenotypes, concentrating on the novel loci. This will establish Xenopus tropicalis as an effective new system to understand ear development and disorders. As described in the Program Announcement, the formation of the human inner ear is complex, and both the normal development and developmental disorders are poorly understood. The understanding of inner ear development will benefit from studies in model organisms such as Xenopus tropicalis, where mutant phenotypes can be used to understand the underlying mechanisms for normal development.